P4.024: Phase 1 Evaluation of Anaphylm Sublingual Film: Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability in Pediatric Patients at High Risk for Allergic Reactions

Background: Prompt administration of epinephrine is essential for managing severe allergic reactions, including anaphylaxis. Dibutepinephrine sublingual film (DESF), currently in development, offers a novel needle-free alternative to epinephrine autoinjectors, potentially improving accessibility and ease of use. This Phase 1 study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of a single 12 mg dose of DESF in pediatric patients with a history of allergic reactions and at high risk of severe allergic events.

Methods: In this multi-center, open-label, Phase 1 trial, 32 pediatric participants (ages 7–17 years, and weighing ≥30 kg) with documented history of allergic reactions received a single sublingual dose of DESF administered by trained site personnel. Plasma epinephrine concentrations were measured to assess PK parameters, including maximum concentration (Cmax) and partial area under the curve (pAUC) at 10, 20, 30 and 45 minutes (pAUC10, pAUC20, pAUC30, pAUC45). PD endpoints, heart rate and blood pressure, were monitored alongside safety assessments, which included treatment-emergent adverse events (TEAEs), changes in vital signs, ECGs, clinical laboratory findings, and oral mucosa evaluations using the Oral Mucositis Assessment Scale (OMAS).

Results: DESF demonstrated rapid absorption and systemic epinephrine exposure, with a mean Cmax of 568.6 and pAUC values of 27.1 (pAUC₁₀), 75.2 (pAUC₂₀), 107.3 (pAUC₃₀), and 143.2 (pAUC₄₅). These PK findings aligned with results from prior adult studies. PD responses showed transient increases in heart rate and blood pressure, consistent with epinephrine’s known effects. DESF was well-tolerated, with no serious adverse events reported. Most TEAEs were mild and self-resolving. OMAS assessments indicated no significant oral mucosal irritation.

Conclusion: In pediatric subjects, DESF demonstrated PK and PD profiles comparable to adult data, along with a favorable safety and tolerability profile. These results support DESF as a promising, non-invasive epinephrine delivery option for the treatment of anaphylaxis in children. The findings are a key component of the New Drug Application (NDA) submitted to the U.S. Food and Drug Administration (FDA), and further highlight DESF’s potential to expand treatment accessibility across a broad age range.